111 research outputs found
Confucian Principles: A Study of Chinese Americans’ Interpersonal Relationships in Selected Children’s Picturebooks
[[abstract]]There has not been enough critical analysis of children’s literature by and about Chinese Americans, especially when compared to other minority groups in the United States. In particular, Chinese American historical books lack extensive analysis. It is important to reflect cultural accuracy in literature and to help children develop clear concepts of self and others by providing precise cultural and physical characteristics of people. While cultural authenticity allows children the opportunity to see a reflection of real experiences within a book instead of seeing stereotypes or misrepresentations, obtaining correct information about a certain time period can help children to see images of immigration accurately represented in literature. Using the Confucian delineation of interpersonal relationships as the major criterion of cultural authenticity, this article examines three currently available children’s picturebooks set in the historical period between 1848 and 1885. In addition to exploring how Chinese Americans’ interpersonal relationships are portrayed in these children’s historical books, this article argues for more proactive inclusion of the diversity in selection of picturebooks.[[notice]]補æ£å®Œ
Electron-Phonon Scattering in Metallic Single-Walled Carbon Nanotubes
Electron scattering rates in metallic single-walled carbon nanotubes are
studied using an atomic force microscope as an electrical probe. From the
scaling of the resistance of the same nanotube with length in the low and high
bias regimes, the mean free paths for both regimes are inferred. The observed
scattering rates are consistent with calculations for acoustic phonon
scattering at low biases and zone boundary/optical phonon scattering at high
biases.Comment: 4 pages, 5 figure
Prime movers : mechanochemistry of mitotic kinesins
Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation
MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice
Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases
Formulating and Solving Sustainable Stochastic Dynamic Facility Layout Problem: A Key to Sustainable Operations
Facility layout design, a NP Hard problem, is associated with the arrangement of facilities in a manufacturing shop floor, which impacts the performance, and cost of system. Efficient design of facility layout is a key to the sustainable operations in a manufacturing shop floor. An efficient layout design not only optimizes the cost and energy due to proficient handling but also increase flexibility and easy accessibility. Traditionally, it is solved using meta-heuristic techniques. But these algorithmic or procedural methodologies do not generate effective and efficient layout design from sustainable point of view, where design should consider multiple criteria such as demand fluctuations, material handling cost, accessibility, maintenance, waste and more. In this paper, to capture the sustainability in the layout design these parameters are considered, and a new Sustainable Stochastic Dynamic Facility Layout Problem (SDFLP) is formulated and solved. SDFLP is optimized for material handling cost and rearrangement cost using various meta-heuristic techniques. The pool of layouts thus generated is then analyzed by Data Envelopment Analysis (DEA) to identify efficient layouts. A novel hierarchical methodology of consensus ranking of layouts is proposed which combines the multiple attributes/criteria. Multi Attribute decision-making (MADM) Techniques such as Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), Interpretive Ranking Process (IRP) and Analytic hierarchy process (AHP), Borda-Kendall and Integer Linear Programming based rank aggregation techniques are applied. To validate the proposed methodology data sets for facility size N=12 for time period T=5 having Gaussian demand are considered
Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice
Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation
Combined immune checkpoint protein blockade and low dose whole body irradiation as immunotherapy for myeloma
BACKGROUND: Multiple myeloma is characterized by the presence of transformed neoplastic plasma cells in the bone marrow and is generally considered to be an incurable disease. Successful treatments will likely require multi-faceted approaches incorporating conventional drug therapies, immunotherapy and other novel treatments. Our lab previously showed that a combination of transient lymphodepletion (sublethal whole body irradiation) and PD-1/PD-L1 blockade generated anti-myeloma T cell reactivity capable of eliminating established disease. We hypothesized that blocking a combination of checkpoint receptors in the context of low-dose, lymphodepleting whole body radiation would boost anti-tumor immunity. METHODS: To test our central hypothesis, we utilized a 5T33 murine multiple myeloma model. Myeloma-bearing mice were treated with a low dose of whole body irradiation and combinations of blocking antibodies to PD-L1, LAG-3, TIM-3, CD48 (the ligand for 2B4) and CTLA4. RESULTS: Temporal phenotypic analysis of bone marrow from myeloma-bearing mice demonstrated that elevated percentages of PD-1, 2B4, LAG-3 and TIM-3 proteins were expressed on T cells. When PD-L1 blockade was combined with blocking antibodies to LAG-3, TIM-3 or CTLA4, synergistic or additive increases in survival were observed (survival rates improved from ~30% to >80%). The increased survival rates correlated with increased frequencies of tumor-reactive CD8 and CD4 T cells. When stimulated in vitro with myeloma cells, CD8 T cells from treated mice produced elevated levels proinflammatory cytokines. Cytokines were spontaneously released from CD4 T cells isolated from mice treated with PD-L1 plus CTLA4 blocking antibodies. CONCLUSIONS: These data indicate that blocking PD-1/PD-L1 interactions in conjunction with other immune checkpoint proteins provides synergistic anti-tumor efficacy following lymphodepletive doses of whole body irradiation. This strategy is a promising combination strategy for myeloma and other hematologic malignancies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40425-014-0043-z) contains supplementary material, which is available to authorized users
Assessing the Effects of Responsible Leadership and Ethical Conflict on Behavioral Intention
[[abstract]]This study develops a research model that elaborates how responsible leadership and ethical conflict influence employees from the perspectives of role theory and attachment theory. Its empirical results reveal that turnover intention indirectly relates to ethical conflict and responsible leadership via the mediating mechanisms of organizational identification and organizational uncertainty. At the same time, helping intention indirectly relates to ethical conflict and responsible leadership only through organizational identification. Finally, the managerial implications for international business and research limitations based on the empirical results are discussed.[[notice]]補æ£å®Œ
Listeria monocytogenes Internalin B Activates Junctional Endocytosis to Accelerate Intestinal Invasion
Listeria monocytogenes (Lm) uses InlA to invade the tips of the intestinal villi, a location at which cell extrusion generates a transient defect in epithelial polarity that exposes the receptor for InlA, E-cadherin, on the cell surface. As the dying cell is removed from the epithelium, the surrounding cells reorganize to form a multicellular junction (MCJ) that Lm exploits to find its basolateral receptor and invade. By examining individual infected villi using 3D-confocal imaging, we uncovered a novel role for the second major invasin, InlB, during invasion of the intestine. We infected mice intragastrically with isogenic strains of Lm that express or lack InlB and that have a modified InlA capable of binding murine E-cadherin and found that Lm lacking InlB invade the same number of villi but have decreased numbers of bacteria within each infected villus tip. We studied the mechanism of InlB action at the MCJs of polarized MDCK monolayers and find that InlB does not act as an adhesin, but instead accelerates bacterial internalization after attachment. InlB locally activates its receptor, c-Met, and increases endocytosis of junctional components, including E-cadherin. We show that MCJs are naturally more endocytic than other sites of the apical membrane, that endocytosis and Lm invasion of MCJs depends on functional dynamin, and that c-Met activation by soluble InlB or hepatocyte growth factor (HGF) increases MCJ endocytosis. Also, in vivo, InlB applied through the intestinal lumen increases endocytosis at the villus tips. Our findings demonstrate a two-step mechanism of synergy between Lm's invasins: InlA provides the specificity of Lm adhesion to MCJs at the villus tips and InlB locally activates c-Met to accelerate junctional endocytosis and bacterial invasion of the intestine
- …